This study investigates the incidence of post-transfusion hepatitis (PTH) in prospectively followed open-heart surgery patients following a variety of measures to interdict infectious donors. These measures have included sequential testing of donors for alanine aminotransferase (ALT), antibody to the Human Immunodeficiency Virus (ANTI-HIV-1), antibody to hepatitis B core antigen (anti-Hbc) and antibody to the hepatitis C virus (anti-HCV) as well as intensive donor questioning in regard to high-risk behavior. Between 1985 and 1990, hepatitis incidence fell from 10% to approximately 3%. Following the introduction of First Generation, anti-HCV testing incidence fell to under 1.5%. We are now following PTH incidence after the use of Second Generation anti-HCV assays and rates are approaching zero among 500 recipients. Greater than 95% of PTS is classified as non-A, non- B hepatitis and approximately 90% of this is HCV related. Because of closure of the NIH open heart surgery program, these studies are being conducted at Georgetown University Hospital (GUH) and Fairfax Hospital.